Targeting neutrophilic inflammation in obstructive airway disease - A narrative review of brensocatib therapy - 22/07/25

Abstract |
Brensocatib is an oral inhibitor of dipeptidyl peptidase 1, an enzyme that activates neutrophil serine proteases. Its potential to reduce neutrophil-driven inflammation has generated interest across a range of chronic inflammatory and respiratory conditions, particularly non-cystic fibrosis (CF) bronchiectasis. As the body of evidence supporting brensocatib continues to expand, there is a clear need for a comprehensive, rigorous, and practical narrative review to consolidate current knowledge and highlight gaps for future research. The aim of this narrative review was to systematically examine and synthesize the existing literature on brensocatib, including its pharmacology, therapeutic applications, clinical trial outcomes, safety profile, and ongoing research efforts. A systematic search was performed across major databases, EMBASE, MEDLINE, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov , through April 2025. Studies involving brensocatib in preclinical or clinical contexts were thoroughly reviewed to evaluate its efficacy and safety. Data were extracted on study design, population, dosage, outcomes, adverse events (AEs), and key findings. The most extensively studied indication was non-CF bronchiectasis, where brensocatib demonstrated a reduction in exacerbation rates and neutrophil protease activity. Preliminary evidence also suggests potential applications in CF, chronic obstructive pulmonary disease, and other neutrophilic conditions. An evaluation of the safety data indicates that the AEs reported are generally mild to moderate in severity. Brensocatib demonstrates potential as a novel anti-inflammatory therapy targeting neutrophil-mediated disease mechanisms. Further research is needed to evaluate its long-term efficacy, safety across a broader population, and its role in combination therapies.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Brensocatib is an oral fifth-generation selective, competitive and reversible inhibitor of DPP-1. |
• | Researchers are studying brensocatib to treat chronic inflammation and respiratory diseases, mainly non-CF bronchiectasis. |
• | Rodent models showed that brensocatib is bioavailable, reduces neutrophilic inflammation, and lowers airway remodeling. |
• | Brensocatib reduced pulmonary exacerbations and sputum NE activity in bronchiectasis patients in the WILLOW and ASPEN trials. |
• | These benefits were achieved while maintaining safety and tolerability, supporting its potential as a long-term therapy. |
Keywords : Brensocatib, Neutrophils, Neutrophil elastase, Dipeptidyl peptidase 1, Bronchiectasis, Inflammation
Abbreviations : AAT, AE, BSI, CatG, CF, CI, COPD, DPP-1, FEV 1 , IL, MAB, MMP, NE, NET, NSP, OAD, PD, PK, PDE, Pr3, ROS, TEAE, T2
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Vol 246
Article 108243- septembre 2025 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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